Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we ...developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection.
Objective: To assess the knowledge and attitude toward coronavirus disease-2019 (COVID-19) among healthcare workers at District 2 Hospital in Ho Chi Minh City (HCMC).Methods: A cross-sectional study ...was performed between January 2020 and February 2020 at District 2 Hospital. A systematic random sampling strategy was carried out and the data was collected through a self-administered questionnaire of the knowledge and attitude of healthcare workers regarding COVID-19. Descriptive analysis was reported to describe the demographic, mean knowledge and attitude score of healthcare workers. Inferential statistics including t-test, ANOVA and Spearman's correlation were used to evaluate the relationship between study variables. Results: A total of 327 eligible healthcare workers had a mean score of knowledge and attitude of 8.17±1.3 (range 4-10) and 1.86±0.43 (range 1-5), respectively. They showed good knowledge and a positive attitude. However, approximately two thirds of the participants knew the mode of transmission, the isolation period and treatment (67.0％, 65.8％, and 58.4％, respectively), and 82.3％ and 79.8％, respectively, held positive attitude regarding the risk of personal and family members getting illness. There was a negative correlation between knowledge scores and attitude scores (r=-0.21, P<0.001). Additionally, healthcare workerspredominately used social media to inform themselves about COVID-19 (91.1％). Conclusions: The majority of healthcare workers had good knowledge and positive attitude toward COVID-19. However, the level of some knowledge and attitude lower than that expected for their position level towards the virus. Additional education interventions and campaigns are required for healthcare workers.
Irritable bowel syndrome (IBS) often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis, but it is not clear ...how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET) was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg) or saline (1:1) was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH), serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline) and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls) by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.
Stress is a known trigger of irritable bowel syndrome (IBS) and exacerbates its gastrointestinal symptoms. However, underlying the physiological mechanism remains unknown. Here, we investigated ...hypothalamic-pituitary-adrenal (HPA) axis, colonic motility, and autonomic responses to corticotropin-releasing hormone (CRH) administration as well as brain activity alterations in IBS. The study included 28 IBS patients and 34 age and sex-matched healthy control subjects. IBS patients demonstrated greater adrenocorticotropic hormone (ACTH) responses to CRH than control subjects. Male IBS patients had greater increases in colonic motility than male HCs after CRH. Female IBS patients showed altered sympathovagal balance and lower basal parasympathetic tone relative to female control subjects. Brain responses to rectal distention were measured in the same subjects using functional magnetic resonance imaging, and their associations with individual ACTH responses to CRH were tested. A negative association between ACTH response to CRH and activity in the pregenual anterior cingulate cortex (pACC) during rectal distention was identified in controls but not in IBS patients. Impaired top-down inhibitory input from the pregenual ACC to the HPA axis may lead to altered neuroendocrine and gastrointestinal responses to CRH. Centrally acting treatments may dampen the stress induced physical symptoms in IBS.
Epstein-Barr virus (EBV) can infect both B cells and epithelial cells. Infection of B cells enables the virus to persist within a host while infection of epithelial cells is suggested to amplify ...viral output. Data from a recent study have shown that the virus shedding in EBV positive individuals is relatively stable over short periods of time but varies significantly over long periods. The mechanisms underlying the regulation of virus shedding within a host are not fully understood. In this paper, we construct a model of ordinary differential equations to study the dynamics of virus shedding into the saliva of infected hosts. Infection of epithelial cells is further separated into infection by virus released from B cells and virus released from epithelial cells. We use the model to investigate whether the long-term variation and short-term stability of virus shedding can be generated by three possible factors: stochastic variations in the number of epithelial cells susceptible to virus released from infected B cells, to virus released from infected epithelial cells, or random variation in the probability that CD8+ T cells encounter and successfully kill infected cells. The results support all three factors to explain the long-term variation but only the first and third factors to explain the short-term stability of virus shedding into saliva. Our analysis also shows that clearance of virus shedding is possible only when there is no virus reactivation from B cells.
► We model virus shedding into saliva of Epstein-Barr virus (EBV) positive individuals. ► Target cells are susceptible to virus released from B cells and epithelial cells. ► Stochastic variation in the number of target cells susceptible to B-cell virus can explain the data. ► Infection of epithelial cells can account for high level of virus shedding. ► Clearance of virus shedding is possible only when there is no virus reactivation from B cells.
Objective: To assess the acceptance of coronavirus disease (COVID-19) vaccine among healthcare workers at two general hospitals in Vietnam when it is available.
Methods: A cross-sectional study was ...conducted using a convenience sampling from January to February 2021 among 410 healthcare workers at two general hospitals in Vietnam via a self-administered questionnaire. A multivariable regression analysis was performed to determine predictors of vaccine acceptance including the demographic factors, COVID-19 knowledge, and vaccine beliefs based on the domains of Health Belief Model.
Results: Among 410 healthcare workers, 76.10% showed vaccination willingness. Predictors of acceptance were determined that the group reporting as "vaccine acceptance" was more likely to be positive towards the perceived susceptibility and severity of COVID-19 (OR 2.45; 95% CI 1.48-4.06, P<0.05), perceived benefits of vaccination, and cues to action (OR 4.36; 95% CI 2.35-8.09, and OR 5.49; 95% CI 2.84-10.61, respectively, all P<0.001), but less likely to have the perceived barriers to vaccination (OR 0.19; 95% CI 0.09-0.38; P<0.001) compared with the no acceptance group. Besides, people who had a good knowledge regarding the severity of illness were 3.37 times more likely to have identified as vaccine acceptance (OR 3.37; 95% CI 1.04-10.86, P<0.05). The demographic factors were also associated with willingness to receive the vaccine, with participants who were staff and received COVID-19 information from relatives were less likely to accept the vaccine over those who were doctors and not receiving information from relatives (OR 0.36; 95% CI 0.13-0.96, and OR 0.37; 95% CI 0.17-0.78, respectively, all P<0.05).
Conclusions: A rate of willingness to get vaccinated against COVID-19 was relatively high with discrepancies between occupation, receiving information from relatives, knowledge toward the severity of illness, and the elements of Health Belief Model. The findings will provide information for the management authorities to develop relevant interventions to promote COVID-19 vaccination uptake.
The human brain responds both before and during the application of aversive stimuli. Anticipation allows the organism to prepare its nociceptive system to respond adequately to the subsequent ...stimulus. The context in which an uncomfortable stimulus is experienced may also influence neural processing. Uncertainty of occurrence, timing and intensity of an aversive event may lead to increased anticipatory anxiety, fear, physiological arousal and sensory perception. We aimed to identify, in healthy volunteers, the effects of uncertainty in the anticipation of uncomfortable rectal distension, and the impact of the autonomic nervous system (ANS) activity and anxiety-related psychological variables on neural mechanisms of anticipation of rectal distension using fMRI. Barostat-controlled uncomfortable rectal distensions were preceded by cued uncertain or certain anticipation in 15 healthy volunteers in a fMRI protocol at 3T. Electrocardiographic data were concurrently registered by MR scanner. The low frequency (LF)-component of the heart rate variability (HRV) time-series was extracted and inserted as a regressor in the fMRI model ('LF-HRV model'). The impact of ANS activity was analyzed by comparing the fMRI signal in the 'standard model' and in the 'LF-HRV model' across the different anticipation and distension conditions. The scores of the psychological questionnaires and the rating of perceived anticipatory anxiety were included as covariates in the fMRI data analysis. Our experiments led to the following key findings: 1) the subgenual anterior cingulate cortex (sgACC) is the only activation site that relates to uncertainty in healthy volunteers and is directly correlated to individual questionnaire score for pain-related anxiety; 2) uncertain anticipation of rectal distension involved several relevant brain regions, namely activation of sgACC and medial prefrontal cortex and deactivation of amygdala, insula, thalamus, secondary somatosensory cortex, supplementary motor area and cerebellum; 3) most of the brain activity during anticipation, but not distension, is associated with activity of the central autonomic network. This approach could be applied to study the ANS impact on brain activity in various pathological conditions, namely in patients with chronic digestive conditions characterized by visceral discomfort and ANS imbalance such as irritable bowel syndrome or inflammatory bowel diseases.
Berberine (BBR) has many pharmacological activities including anti-inflammatory, antibacterial, and against many diseases, especially cancer. However, berberine is a large molecular compound with ...rapid metabolism by enzymes in the human body and limited bioavailability. To improve, berberine needs to be coated and combined with other active ingredients. In this study, berberine is successfully encapsulated by coaxial electrosprayed chitosan (CS) without cross-linked agents, and piperine (PPR) is also added via two different approaches to improve absorption and bioavailability. The obtained nanoparticles have a spherical shape with smooth surface and relatively wide particle size distribution observed by SEM. The uniform core/shell structure with clear boundary, non-agglomerated encapsulated spheres, and average diameter of 143.67 ± 56.16 nm (for BBR-PPR@CS) and 152.91 ± 48.50 nm (for BBR@PPR-CS) were analyzed by TEM images. The appearance of some weak peaks and slight shifting of major peaks in FTIR spectra of BBR-PPR@CS and BBR@PPR-CS samples and their high encapsulation efficiencies reflected their successful encapsulation. In drug release experiments, as expected, with the combination of PPR and CS in the outer shell (BBR@PPR-CS), the release of PPR was faster than that of BBR. The amount of drug in all samples was released more strongly at pH 5.0 than at pH 7.4, and the release time extended up to 36 h. Therefore, coaxial electrosprayed chitosan nanoparticle is a promising functional material for the simultaneous encapsulation of BBR and PPR, as well as increasing bioavailability of BBR, contributing to the development of controlled drugs toward effective anticancer.
Graphical abstract
Interoceptive fear learning and generalization have been hypothesized to play a key role in unexplained abdominal and esophageal pain in patients with functional gastrointestinal disorders. However, ...there is no experimental evidence demonstrating that fear learning and generalization to visceral sensations can be established in humans and alter visceral perception.
In a novel fear learning-generalization paradigm, an innocuous esophageal balloon distension served as conditioned stimulus (CS), and distensions at three different pressure levels around the pain detection threshold were used as generalization stimuli. During fear learning, the CS was paired with a painful electrical stimulus (unconditioned stimulus) in the conditioning group (n = 30), whereas in the control group (n = 30), the unconditioned stimulus was delivered alone. Before and after fear learning, visceral perception thresholds for first sensation, discomfort, and pain and visceral discrimination sensitivity were assessed.
Fear learning was established in the conditioning group only (potentiated eye-blink startle to the CS (t(464.06) = 3.17, p = .002), and fear generalization to other stimulus intensities was observed (t(469.12) = 2.97, p = .003; t(464.29) = 4.17, p < .001). The thresholds for first sensation habituated in the control group, whereas it remained constant in the conditioning group (F(1,43) = 9.77, p = .003).
These data show that fear learning using visceral stimuli induces fear generalization and influences visceral perception. These findings support the idea that in functional gastrointestinal disorder, fear learning and generalization can foster gastrointestinal-specific anxiety and contribute to visceral hypersensitivity.
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